Deconstructing signal transduction pathways that regulate the actin cytoskeleton in dendritic spines

Abstract

Dendritic spines are the sites of most excitatory synapses in the central nervous system. Recent studies have shown that spines function independently of each other, and they are currently the smallest known processing units in the brain. Spines exist in an array of morphologies, and spine structure helps dictate synaptic function. Dendritic spines are rich in actin, and actin rearrangements are critical regulators of spine morphology and density. In this review, we discuss the importance of actin in regulating dendritic spine morphogenesis, and discuss the upstream signal transduction pathways that either foster or inhibit actin polymerization. The understanding of actin regulatory pathways is best conceptualized as a hierarchical network in which molecules function in discrete levels defined by their molecular distance to actin. To this end, we focus on several classes of molecules, including guanine nucleotide exchange factors, small GTPases, small GTPase effectors, and actin binding proteins. We discuss how individual proteins in these molecular classes impact spine morphogenesis, and reveal the biochemical interactions in these networks that are responsible for shaping actin polymerization. Finally, we discuss the importance of these actin regulatory pathways in neuropsychiatric disorders. © 2012 Wiley Periodicals, Inc.

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“…A major component of these postsynaptic structures is the actin cytoskeleton, which is a key regulator of spine morphology (Fig. 3) (Fischer et al, 1998;Hotulainen et al, 2009); tight control of the actin cytoskeleton is crucial to proper synaptic function (Yoshihara et al, 2009;Hotulainen and Hoogenraad, 2010;Penzes and Cahill, 2012). But what are the putative molecular mechanisms that connect extracellular signals, such as estrogens, to the remodeling of dendritic spines?…”

Структура Скелетних М’язів Після Гіпокінезії І Фізичного Навантаження Середньої Аеробної Потужності

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“…Above all things it touches the estimation of such intercommunications between muscle fibers and blood vessels [10][11][12]. Functional integrity of these components is confirmed by the results of research of muscles pathology after protracted hypokinesia, where most authors specify on the expressed changes of ultrastructural vehicle of nervous fibres [9]. However, works devoted to influence of protracted hypokinesіa on the organism of different animals and man pay not enough attention to research of posthypokinetic reactions in muscle fibers and wall of blood vessels is spared undeservedly [1,3,11,12].…”

“…Limitation of motive activity on the method [9] offered by us, term of hypokinesia 300 days. The physical loadings were designed in tredmile ( daily trainings during 15 minutes at speed at run 20 m/min during 30 days).…”

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“…Rac activity also controls actin dynamics. The small GTPase activity itself is under the control of GEFs, which serve as activators of small GTPases [25]. Inhibition of the expression or function of upstream regulators of the actin cytoskeleton, including Rac-GEFs, Rac, and Rac targets such as PAK, cause the loss of spines [26][27][28][29].…”